Chemical syntheses and in vitro antibacterial activity of two desferrioxamine B-ciprofloxacin conjugates with potential esterase and phosphatase triggered drug release linkers

被引：78

作者：

Ji, Cheng ^{[1
]}

Miller, Marvin J. ^{[1
]}

机构：

[1] Univ Notre Dame, Dept Chem & Biochem, Notre Dame, IN 46556 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2012年 / 20卷 / 12期

基金：

美国国家科学基金会;

关键词：

Iron transport; Antibiotics; Siderophore conjugates; Drug delivery; Drug release; HYDROXY AMIDE LACTONIZATION; INFECTIOUS-DISEASES SOCIETY; SENSITIVE CYCLIC PRODRUG; GRAM-NEGATIVE BACTERIA; STEREOPOPULATION CONTROL; RATE ENHANCEMENT; PSEUDOMONAS-AERUGINOSA; ESCHERICHIA-COLI; AMINE PRODRUGS; ACIDS;

D O I：

10.1016/j.bmc.2012.04.034

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Two desferrioxamine B-ciprofloxacin conjugates with 'trimethyl-lock' based linkers that are designed to release the antibiotic after esterase or phosphatase-mediated hydrolysis were synthesized. The potential esterase-sensitive conjugate 13 displayed moderate to good antibacterial activities against selected ferrioxamine-utilizing bacteria, although the activities were lower than the parent drug ciprofloxacin. However, the potential phophatase-sensitive conjugate 23 was inactive against the same panel of organisms tested. These properties appeared to be related to the activating efficiency of the linker by the enzyme and to the outer membrane protein recognition of the chemically modified siderophore used in the conjugate. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：3828 / 3836

页数：9

共 38 条

[1] AMINE PRODRUGS WHICH UTILIZE HYDROXY AMIDE LACTONIZATION .2. A POTENTIAL ESTERASE-SENSITIVE AMIDE PRODRUG [J].

AMSBERRY, KL ;

GERSTENBERGER, AE ;

BORCHARDT, RT .

PHARMACEUTICAL RESEARCH, 1991, 8 (04) :455-461

[2] AMINE PRODRUGS WHICH UTILIZE HYDROXY AMIDE LACTONIZATION .1. A POTENTIAL REDOX-SENSITIVE AMIDE PRODRUG [J].

AMSBERRY, KL ;

BORCHARDT, RT .

PHARMACEUTICAL RESEARCH, 1991, 8 (03) :323-330

[3] PERIPLASMIC ENZYMES IN GRAM-NEGATIVE BACTERIA [J].

BEACHAM, IR .

INTERNATIONAL JOURNAL OF BIOCHEMISTRY, 1979, 10 (11) :877-883

[4] STEREOPOPULATION CONTROL .2. RATE ENHANCEMENT OF INTRAMOLECULAR NUCLEOPHILIC DISPLACEMENT [J].

BORCHARD.RT ;

COHEN, LA .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1972, 94 (26) :9166-9174

[5]

Bornscheuer UT, 2002, FEMS MICROBIOL REV, V26, P73, DOI 10.1111/j.1574-6976.2002.tb00599.x

[6] Bad Bugs, No Drugs: No ESKAPE! An Update from the Infectious Diseases Society of America [J].

Boucher, Helen W. ;

Talbot, George H. ;

Bradley, John S. ;

Edwards, John E., Jr. ;

Gilbert, David ;

Rice, Louis B. ;

Scheld, Michael ;

Spellberg, Brad ;

Bartlett, John .

CLINICAL INFECTIOUS DISEASES, 2009, 48 (01) :1-12

[7] INTRACELLULAR ACTIVATION OF ALBOMYCIN IN ESCHERICHIA-COLI AND SALMONELLA-TYPHIMURIUM [J].

BRAUN, V ;

GUNTHNER, K ;

HANTKE, K ;

ZIMMERMANN, L .

JOURNAL OF BACTERIOLOGY, 1983, 156 (01) :308-315

[8] Sideromycins: tools and antibiotics [J].

Braun, Volkmar ;

Pramanik, Avijit ;

Gwinner, Thomas ;

Koeberle, Martin ;

Bohn, Erwin .

BIOMETALS, 2009, 22 (01) :3-13

[9] REDUCTIVE LACTONIZATION OF STRATEGICALLY METHYLATED QUINONE PROPIONIC-ACID ESTERS AND AMIDES [J].

CARPINO, LA ;

TRIOLO, SA ;

BERGLUND, RA .

JOURNAL OF ORGANIC CHEMISTRY, 1989, 54 (14) :3303-3310

[10] FORMATION AND HYDROLYSIS OF LACTONES OF PHENOLIC-ACIDS [J].

CASWELL, M ;

SCHMIR, GL .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1980, 102 (14) :4815-4821

← 1 2 3 4 →